This article first appeared in Acupuncture in Medicine (December
1999, vol.17(2), p.124)

Introduction

As anyone who has practised acupuncture for even quite a short time will
know, unexplained laughter or tears, though a little unusual, occur from
time to time and can be quite striking and prolonged. We often attribute
these things to release of endogenous opioids, but there's not much
direct evidence to support this idea, and one fact which counts against
it is the observation that the response usually occurs very rapidly
after the needles are inserted, even within seconds; too soon, one might
think, for a humoral effect of that kind.

Something that is seen more frequently than actual laughter or tears is
euphoria. Some patients may report that they feel "high", as if they
have taken alcohol or other mood-altering drugs. This, again, is often
attributed to release of endogenous opioids, but the same comments
apply. Marked euphoria is not particularly common, but minor versions of
it, generally described as a sense of calm or relaxation, occur in
probably 30 or 40 per cent of cases.

Another effect, which is fortunately much less common than those I've
just described, is an epileptic fit. These generally happen in patients
who are not known to be epileptic. When they occur in patients who were
sitting at the time they are usually attributed to vasovagal syncope
causing temporary cerebral anoxia, but this may not be the whole story
since they can also occur in patients who are lying down.

It is well known that patients who are unwilling to have acupuncture or
are afraid of it seldom respond well to treatment; this has been noted
in the traditional literature for many centuries. (On the other hand,
belief in the efficacy of the treatment is unimportant).

All these things must, presumably, have a neurological explanation. They
point to the occurrence of events in the central nervous system that
have an effect on mood and behaviour, and what I should like to do is to
think about some of the brain structures that may be involved.

Much of the current theorising about acupuncture concentrates on the
spinal cord and brain stem, with particular reference to pain(2).
However, this does not tell us much about the subjective phenomema of
euphoria and so forth, so I think it is also the higher levels that we
ought to be looking at, particularly the limbic system.

There is a widespread idea that this is a part of the brain that is
closely concerned with emotion, so it might reasonably be thought to
have something to do with unexplained laughter and tears, as well as
with fear and euphoria. Actually, the idea that the limbic system is
concerned with emotion is at best a half-truth, but there certainly is a
connection, which is probably relevant to acupuncture. But before
getting down to this we need to establish exactly what it is we're
talking about here, because the limbic system is a rather slippery
concept.

Anatomically, the main structures we have to consider become visible
only when we split the brain sagitally into two halves and look at the
inner or medial surface (3).

The limbic system is made up of the limbic lobe and certain additional
structures.

The limbic lobe is on the inner aspect of the
cortex, It partially surrounds the corpus callosum and is made up of the
cingulate (which means belt-like) gyrus and the parahippocampal gyrus.
These are connected to each other by a narrow isthmus beneath the
splenium (posterior part) of the corpus callosum. The hippocampus, which
is in the floor of the temporal horn of the lateral ventricle, is also
included in the limbic lobe.

"Limbic" means "rim", as in the rim of a tennis racquet. One might
wonder how the limbic lobe got that name, because in the human brain it
is not all that conspicuous owing to the huge development of the cortex,
but in other mammals, for example the rabbit, it forms a considerable
part of the medial aspect of the hemisphere and really is a kind of rim,
as the name implies. This was why Paul Broca coined the term in the 19th
century. It was an anatomical, not a functional, description. Later this
part of the brain was thought to be concerned with smell and was
therefore called the rhinencephalon (meaning "nose brain").

The amygdala

This is a group of nuclei situated in the anterior part of the temporal
lobe, lying between the anterior end of the temporal horn of the lateral
ventricle and the ventral surface of the lentiform nucleus. Some of them
are olfactory but most are involved in the limbic system.

The hippocampus

This forms an elevation in the floor of the temporal horn of the lateral
ventricle. If you trace the structure outwards, towards the surface of
the brain, you find that it is continuous with the parahippocampal gyrus
at the inferiomedial surface of the temporal lobe; the hippocampus, in
other words is a cortical structure.

To understand how this works, we need to take account of embryology and
also the evolutionary history of the brain (4). What happens during its
development is that the free margin of the developing brain (the
pallium) becomes rolled upwards and then inwards to form the
hippocampus. The part that is still at the surface, so to speak, is the
parahippocampal gyrus. This folding process continues, now in the
opposite direction, taking the free margin of the developing
hippocampus outwards again, towards the medial surface of the temporal
lobe. In this way the free margin of the hippocampus becomes doubled out
and forms the dentate gyrus, which is separated from the parahippocampal
gyrus by the hippocampal sulcus. ("Dentate" refers to the fact that its
margin is serrated.) As a result of this repeated folding the mature
hippocampus comes to consist of two interlocking sections of tubes. In
cross-section it looks rather like a swiss roll. Hence we can speak of
the hippocampal formation, consisting of the hippocampus, the dentate
gyrus, and most of the parahippocampal gyrus.

The name hippocampus means seahorse, but I think myself that it more
closely resembles a scorpion without legs. The head of the scorpion lies
close to the amygdala at the tip of the temporal lobe and the body
extends posteriorly, ending below the splenium of the corpus callosum.
The tail of the scorpion is represented by a band of efferent and
afferent fibres which form a ridge along its medial border called the
fimbria. The left and right fimbriae continue as the crura of the
fornix, which run from the hippocampus backwards, upwards, and then
forwards beneath the corpus callosum. The "tails" of the two
hippocampuses, i.e the two fimbriae, join up for a time to form the body
of the fornix before separating again to descend as the columns of the
fornix and finally reach the mammillary bodies of the hypothalamus on
each side.

Histologically, the parahippocampal gyrus is 6-layered or almost so
(i.e. neocortex) but the hippocampus is 3-layered (archicortex); there
is a transition in structure at the "bend" called the subiculum. The
pyramidal cell layer of the hippocampus is continuous with layer 5
(internal pyramidal) of the cortex. Certain of the hippocampal cells are
thought to show an effect called longterm potentiation (LTP), which
lasts for several days and is believed to be involved in the formation
of new memories.

The hippocampus varies in size in different animals and reaches
its largest absolute and relative size in humans. This suggests
that it has some important role in human consciousness.

Pathology

The hippocampus is frequently damaged in disease (4). It is classified
in three sectors, and the cells in the first of these (CA 1) are
particularly sensitive to oxygen deprivation. Temporary loss of oxygen
supply is thought to be the cause of transient global amnesia. More
prolonged loss, if bilateral, results in permanent failure to make new
memories. Cells in CA 1 are affected early in Alzheimer's disease. The
limbic system has been implicated in schizophrenia; there is reduction
in the size of the amygdala, hippocampus, and parahippocampal gyrus.

Functional implications

These facts suggest that the hippocampus, and the limbic system
generally, are closely connected with memory formation. So why do
we have this idea that they are connected with emotion?

To understand this, we have to see how the limbic system idea has
developed (4).

A brief historical digression

At the end of the 19th century the philosopher and psychologist
William James put forward a theory of emotion which seemed at
first glance paradoxical.

Common sense says that, when you see a bear in the wood (James's
example), you feel frightened: your stomach churns, you start to sweat,
and you run away. This implies that the emotion of fear causes the
physical effects. James however said that, when you see the bear, this
directly causes the physical effects of sweating, churning stomach, and
running away, and it is the awareness of these physical events that
constitutes the feeling of fear. In other words, in James's view the
emotion is caused by the physiological changes, not the other way about.

In the 1920s Walter Cannon and Philip Bard put forward a somewhat
similar theory. They suggested that seeing the bear causes changes in
the thalamus; these in turn are transmitted to the hypothalamus and
thence to the muscles and organs, and it's the events in your brain that
are perceived as fear. (This is the famous "fright and flight"
reaction.) In other words, they moved the centre of interest from the
periphery to the brain, and especially the hypothalamus.

Cannon disagreed with James's idea but in fact his own theory
isn't all that different; it just focuses on different physiological
phenomena.

There was however apparently a difficulty with this theory: the
cortex was thought not to be directly connected to the
hypothalamus, so how could changes in the hypothalamus reach
consciousness?

Then in 1937 James Papez put forward a new theory which was destined to
become very influential. He went back to Broca's notion and suggested
that the limbic lobe was responsible for emotion. Information was
supposed to flow in a circuit from the hypothalamus to the medial cortex
and back again.

In it, the cingulate gyrus has
a central role; it is supposed to be "emotional cortex" and analogous to
the sensory cortex in the parietal lobe. The hippocampus is also
concerned with emotion. This was a mistake, but nevertheless the theory
was a brilliant anticipation of later anatomical discoveries.

Paul MacLean took up the Papez theory in 1949 and elaborated it. He
suggested that the hippocampus was what he called an "emotional
keyboard" (a bit like the Organ of Corti?). He continued to elaborate
this idea as the years went by and in 1970 he introduced the notion of
the "triune brain", made up as follows:

Reptilian brain = brainstem reticular system and basal
ganglia

Old mammalian brain = limbic system

New mammalian brain = neocortex

Emotional and psychological disorders were supposed to be due to
faulty communication between the old and new parts of the brain.
This theory was popularized by Arthur Koestler, who used it to
diagnose what was amiss with modern society.

So where does all this leave the limbic system today?

Today, the limbic system idea is generally accepted by brain
scientists. Textbooks of neuroanatomy contain a chapter on it.
Lay dictionaries have an entry for it. Nevertheless, it has important
defects.

On the merit side, it sets emotion in an evolutionary context, and it
may explain some of the psychiatric symptoms (dissociation of intellect
and emotion) that MacLean claimed it did. But the distinction between
"old" and "new" cortex is no longer accepted (for this reason, some
authorities now prefer to avoid terms like "neocortex" and "archicortex"
and speak of "isocortex" and "allocortex" instead). It also appears that
the forebrain is actually phylogenetically older than the midbrain and
hindbrain (14). Moreover, damage to the hippocampus and mamillary bodies
has little effect on emotion but a great deal of effect on memory,
contrary to what MacLean predicted.

So why has the theory survived so long? Partly because it is a
convenient shorthand to name the areas between the hypothalamus and
"neocortex", and partly because these structures, especially the
amygdala, do have something to do with emotion; the theory is not
completely wrong. But to call the limbic system the emotional centre of
the brain is certainly misleading (5,6).

The limbic system and acupuncture

With this clarification out of the way, I want to pass on to consider
how acupuncture may be thought to modify the activity of the limbic
system. I want to suggest that acupuncture is capable of modifying the
activity of the limbic system so as to give rise to the various
phenomena I mentioned at the beginning, but, first, one question: is it
plausible to suggest that acupuncture could actually modify brain
function in this way? I think it is, if we remember than much of the
limbic system (anterior cingulate, hippocampus) is cortical or derived
from cortex. Cortical representation is a lot more plastic than we
realized a few years ago, and what is particularly interesting in the
present context is that painful stimulation seems to be unusually
effective in this regard.

I'll give just one example (7). In a recent study, healthy volunteers
were given tactile stimulation to the right side of the lower lip for a
few minutes. Then they were given painful electrical stimulation to the
median nerve on the same side. When the lip stimulation was repeated,
some of them felt this both at the lip and at the site in the wrist
where the painful stimulus had been applied; one of these subjects
actually felt that her fist was clenched. This of course is something
that patients with phantom limbs sometimes report. So this study
suggests that even brief peripheral painful stimulation can temporarily
alter sensory cortical mapping. I therefore find it quite plausible to
suppose that it can also modulate activity in the anterior cingulate
cortex and other limbic system structures.

Emotion

Although we now know that the hippocampus is concerned with memory, the
amygdala is indeed involved in emotion, especially fear (5).

If both temporal lobes are removed from animals they
become abnormally tame and are also hypersexual.
They put all sorts of things in their mouths because
they are unable to decide, from sight, if things are
suitable to eat (Kluver-Bucy syndrome).

In humans, stimulation of the amygdala produces
feelings of fear or anger, which suggests that activity
in the amygdala causes the autonomic and somatic
accompaniments of these emotions.

The amygdala (and other parts of the nervous system)
have many post-synaptic receptors for which
gamma-aminobutyric acid (GABA) is an inhibitory
neurotransmitter, and diazepam and other anxiolytics
mimic the action of GABA at these sites.

Fear conditioning in animals (rather similar to Pavlovian
conditioning but using innate fear-producing responses)
results in very long-lasting effects which, unlike the
responses produced by Pavlovian techniques, are probably
permanent and are mediated by the amygdala.

Seizures originating in this area are associated with
emotions, especially fear.

These facts about the amygdala suggest the following hypotheses:

Part of the calming effect of acupuncture may be due to
release of GABA in the amygdala and other limbic system
areas.

The reason why acupuncture doesn't work in patients who
are afraid of it may be that their amygdalas are primed
by early experiences of pain associated with needles so
that they always react badly in similar situations (a
form of fear conditioning).
Belief, on the other hand, is a cortical phenomenon and
does not affect this pathway directly.

Predictions

Imaging studies should show increased activation of the
temporal lobes in strong reactors.

Animal studies should show that acupuncture causes
release of GABA in the amygdala.

If patients who failed to respond to acupuncture because
they were afraid of it were given diazepam (Valium) they might
become better responders temporarily.

Strong reactors

Why is it that some people react very strongly to acupuncture
while others don't seem to react at all?

Professor Thompson and his colleagues (8) have found that patients
differ considerably in their responses to transcutaneous electrical
nerve stimulation (TENS). Individual patients tend to have preferred
frequency of stimulation and pattern of stimulation, which is constant
for those individuals, so these authors suggest that lack of response to
TENS may be linked to low central nervous system responsiveness to
sensory stimuli in general. It seems plausible that the same is true of
acupuncture sensitivity. Strong reactors would then be people whose
central nervous system, including the limbic system, is particularly
sensitive to sensory stimulation. In the case of the limbic system there
are nociceptive receptors in the cingulate cortex that have large
receptive fields that may encompass the whole body (9). Strong reactors
may therefore be people with many such receptors.

What about euphoria?

Here we may get a clue from experiments in which Ketter and colleagues
used intravenous injection of procaine to modify the activity of the
limbic system and related structures in normal subjects (10). Some of
these people experienced euphoria, which was related to reduced activity
in the left amygdala. Visual and auditory hallucinations also occurred.
Regional cerebral blood flow increased in anterior paralimbic
structures, particularly areas related to the amygdala. These authors
remark that there are also reports of euphoria also being caused by
stimulation of the anterior cingulate cortex.

What all this suggest is that strong reactors may be people in
whom these structures are more easily influenced by sensory
stimulation, either to depress the amygdala or to stimulate the
anterior cingulate.

Predictions

They may be more inclined to religious belief.
(These overlap with Mann's impression that they are
artistic, etc.) (11)

Strong reactors should show an increased incidence of a
history of out-of-body experiences and hallucinations.

A correspondent has recently told me of a case that seems to support
this idea. She writes as follows:

I have been treating a relative for Liver Wind
(manifesting as one tonic-clonic seizure followed by
periods of intense dizziness, which have ceased during
six weeks or so of conventional medication and regular
acupuncture/moxa). I believe the Liver Wind stems
from long term Liver Qi Stagnation and also Liver
Blood deficiency.

In the last four treatments I have used LI4 and LR3,
plus sometimes SP6, and always moxa on KI1. He
dislikes needles (but suffers them!), but has always
reported great effect from the moxa, such as feeling a
sensation connect his feet to his head, and says it
makes him very relaxed. He has also reported feeling
what I would call more grounded between treatments -
he says when he is walking he feels he is more in his
hip area than his head.

In the last treatment (as above, no SP6) he reported,
towards the end of the moxa session, feeling like he
had left his body, and been floating. He had felt
himself turn around until his feet were nearly by the
head of his body, and then back, and then rotate to
his left so he was on his left side, and then back
again. I stopped treatment, and he said he was back
where he should be and feeling great.

My correspondent says that her relative enjoyed the out-of-body
experience so much that he was reluctant to mention it in case she
stopped the treatment! The neurologist confirmed that the "dizziness"
episodes were minor absences; they have ceased after the patient
started taking carbamazepine.

A report has recently appeared describing out-of-body experiences
produced by brain stimulation at the right anglular gyrus in a patient
who was undergoing evaluation for epilepsy treatment (1). The patient had
right temporal-lobe epilepsy. The authors suggest that the experience
of dissociation of self from the body is a result of failure to
integrate complex somatosensory and vestibular information.

Epilepsy

Although it is rare, some patients have fits during acupuncture.

All the structures we have been considering are frequently implicated in
epilepsy, especially epilepsy with strange subjective phenomena not
necessarily accompanied by loss of consciousness. This is called complex
partial epilepsy, or temporal lobe epilepsy. Temporal lobe epilepsy can
cause difficulties in speaking, and I've noticed that some strong
reactors also seem to find a certain degree of this while being needled.

There are similarities between temporal lobe epilepsy and some kinds of
migraine aura, and the fact that acupuncture seems to help some patients
who suffer from migraine with aura may be connected with this. Moreover,
the authors of the procaine study I cited just now say that patients
with anxiety disorders report an increased incidence of spontaneous
paroxysmal and emotional phenomena similar to those of patients with
complex partial epilepsy, which may be due to limbic dysfunction (10).

Implications:

Epilepsy occurring in acupuncture may at times be due to activation of
the temporal lobes via their connections with the amygdala and
hippocampus. Although frank fits are unusual, some of the phenomena that
acupuncture patients report may be very minor versions of the same
process. For instance, one 30-year-old epileptic woman experienced a
warm sensation in both feet ascending through the legs (2). Similar
sensations are described from time to time by acupuncture patients and
are ascribed by traditionalists to the flow of chi.

Predictions

epilepsy should be more likely to occur in strong
reactors.

strong reactors should show EEG changes in their
temporal lobes during acupuncture to a greater extent
than other patients, even when not suffering fits.

Laughter and tears

>
Not much is known about how laughter is produced by the brain.
Papez and later writers have claimed that it is a motor program
organized by the limbic system and brain stem.

Arroyo and colleagues have described three patients with seizures who
shed light on this question (12). In one, the onset of seizures was in
the left anterior cingulate region. This patient didn't feel amused
although she was laughing. The other two didn't laugh during seizures
but laughter was elicited by electrical stimulation of the
parahippocampal gyrus and neighbouring cortex, and both of these
actually felt amused during stimulated laughter.

These observations suggest that laughter can be produced by
activation of parts of the limbic system, though there
differences according to the exact site of stimulation.

Laughter without subjective amusement can be produced by
seizures starting in the anterior cingulate region.

Electrical stimulation of the basal temporal lobe
can cause laughing accompanied by a sense of amusement.

One possibility, therefore, is that acupuncture simply activates
those parts of the limbic system that are involved in the
production of laughter or tears. Presumably it does this in a
relatively "normal" way, since patients generally do feel amused
or euphoric when this occurs.

However, there is also another possibility, based on a suggestion
by Ramachandran (13).

Patients with a condition called pain asymbolia feel pain but don't
experience the emotional accompaniment. Moreover, some patients with
this disorder giggle when pricked. This, of course, is exactly what
happens in acupuncture. So it's tempting to see a clue to why
acupuncture causes laughter here, but there is a problem: pain asymbolia
is pathological; it may be due to damage to the insular cortex, which
receives pain input and projects to the anterior cingulate cortex,
whereas acupuncture-related laughter usually occurs in the presence of
an intact nervous system. We might suppose that acupuncture can
temporarily disconnect the insular cortex from the anterior cingulate,
to produce a kind of temporary "pain asymbolia".

There is, however, also another idea, again based on a hypothesis put
forward by Ramachandran about the reason we laugh when we are tickled.
He thinks that laughter generally occurs when we perceive an
incongruity; this is the basis of many jokes and also the reason we may
laugh when a pompous man slips on a banana skin. Ramachandran suggests
that they perceive an incongruity between an apparent physical threat
and a context of play; this makes them laugh. This theory explains why
one can't easily tickle oneself; one knows in advance that there is no
threat involved.

Now, acupuncture is also a kind of physical threat, in that (relatively
minor) pain is inflicted but in a therapeutic context. Also, one may
expect the needle to be painful and then be pleasantly surprised when
it's not as bad as expected. There may thus be a functional dissociation
between the insula and the anterior cingulate cortex. The insular cortex
registers the needle prick as a threat but the cingulate cortex doesn't
agree, hence there is a perceived incongruity resulting in laughter. On
this hypothesis, acupuncture is a kind of tickling.

Predictions

Patients who laugh when having acupuncture should find
the procedure pain-free or nearly so (because severe
pain would be likely to over-ride the dissociation).

They are also likely to be especially ticklish.

Part of the pain relief that acupuncture can produce may
be due to dissociation between the sensation of pain and the emotional
distress that it normally causes; patients may continue to feel pain but
be less bothered by it. This is something we could look for by means of
suitably designed questionnaires.

Memory

In view of the role of the limbic system, and especially the
hippocampus, in memory formation one might expect that acupuncture would
have some effects on this. In fact, I have recently heard of someone who
finds that he is unable to access memories while having acupuncture.
This is an area which would repay further research and observation; for
example, what are the effects of acupuncture in patients suffering from
Alzheimer's disease?

Conclusions

Some acupuncture effects may be due to events in the limbic
system

certain predictions follow from this hypothesis and
should allow it to be tested.

we need to know more about the personality and
physiological characteristics of strong reactors; at
present this is at the level of anecdote.

This may all take some time to carry out, but I think that if we
are to arrive at a reasonably comprehensive explanation of how
acupuncture works we will need to take account of the role of the
limbic system.

In the meantime, I find that if one reflects on what is known
about this very complex system it does shed light on some of the
more curious phenomena which we encounter from time to time while
needling our patients.

Acknowledgements

I should like to express my warm thanks to Professor Thompson, who read
an early draft of this paper and encouraged me to continue with it; he
also very kindly provided some illustrations, references, and reprints
of his papers. I need hardly say that he is not responsible for any
errors I may have stumbled into. I am also grateful to my son Robert,
who is a neuroscience student and was able to obtain some invaluable
reference material for me.